Opioid tolerance and pain hypersensitivity associated with mTOR activation

Currently, opioids are the standard treatment for chronic pain. Patients on opioids for long periods of time become desensitized to these drugs or become paradoxically hypersensitive to pain (hyperalgesia); however, the adaptive mechanisms are not well understood.

In this issue of the Journal of Clinical Investigation, Yuan-Xiang Tao and colleagues from the New Jersey Medical School at Rutgers University report that the protein mTOR, which is a global regulator of translation, plays a major role in morphine tolerance. Using animal models of opioid exposure, the authors found that mTOR is highly expressed in neurons of the dorsal horn, which is where opioid desensitization and are thought to originate. Inhibition of mTOR activity with the drug rapamycin prevented and treated opioid tolerance and hyperalgesia in rats that had been exposed to chronic morphine injections.

Chronic morphine injection increased activity of mTOR and two of its in the neurons of the dorsal horn. Furthermore, the authors determined that mTOR links a key opioid receptor to downstream proteins that are known to be involved in and hyperalgesia, and that blocking mTOR reduced the production of these proteins.

This study details a potential mechanism that drives opioid desensitization and hyperalgesia and suggests that targeting the mTOR pathway may improve pain management

More information: J Clin Invest. DOI: 10.1172/JCI70236

Related Stories

Recommended for you

FDA clears drug for leading form of cystic fibrosis

date Jul 02, 2015

Federal health officials have approved a new combination drug for the most common form of cystic fibrosis, the debilitating inherited disease that causes internal mucus buildup, lung infections and early death. But it will ...

User comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.